tbuckley/cabot-search huggingface dataset:
Ganglioside GM3 Protects Against Abdominal Aortic Aneurysm by Suppressing Ferroptosis
Authors: Fangni Zhang, Kan Li, Wenhui Zhang, Ziyan Zhao, Fangyuan Chang, Jie Du, Xu Zhang, Kaiwen Bao, Chunyong Zhang, Lei Shi, Zongwei Liu, Xiangchen Dai, Chen Chen, Dao Wen Wang, Zhong Xian, Hongfeng Jiang, Ding Ai
Journal: Circulation (2023)

Abdominal aortic aneurysm (AAA) is a potentially life-threatening vascular condition, but approved medical therapies to prevent AAA progression and rupture are currently lacking. Sphingolipid metabolism disorders are associated with the occurrence and development of AAA. It has been discovered that ganglioside GM3, a sialic acid-containing type of glycosphingolipid, plays a protective role in atherosclerosis, which is an important risk factor for AAA; however, the potential contribution of GM3 to AAA development has not been investigated. We performed a metabolomics study to evaluated GM3 level in plasma of human patients with AAA. We profiled GM3 synthase (ST3GAL5) expression in the mouse model of aneurysm and human AAA tissues through Western blotting and immunofluorescence staining. RNA sequencing, affinity purification and mass spectrometry, proteomic analysis, surface plasmon resonance analysis, and functional studies were used to dissect the molecular mechanism of GM3-regulating ferroptosis. We conditionally deleted and overexpressed St3gal5 in smooth muscle cells (SMCs) in vivo to investigate its role in AAA. We found significantly reduced plasma levels of GM3 in human patients with AAA. GM3 content and ST3GAL5 expression were decreased in abdominal aortic vascular SMCs in patients with AAA and an AAA mouse model. RNA sequencing analysis showed that ST3GAL5 silencing in human aortic SMCs induced ferroptosis. We showed that GM3 interacted directly with the extracellular domain of TFR1 (transferrin receptor 1), a cell membrane protein critical for cellular iron uptake, and disrupted its interaction with holo-transferrin. SMC-specific St3gal5 knockout exacerbated iron accumulation at lesion sites and significantly promoted AAA development in mice, whereas GM3 supplementation suppressed lipid peroxidation, reduced iron deposition in aortic vascular SMCs, and markedly decreased AAA incidence. Together, these results suggest that GM3 dysregulation promotes ferroptosis of vascular SMCs in AAA. Furthermore, GM3 may constitute a new therapeutic target for AAA.
Flipped C-Terminal Ends of APOA1 Promote ABCA1-Dependent Cholesterol Efflux by Small HDLs
Authors: Yi He, Chiara Pavanello, Patrick M. Hutchins, Chongren Tang, Mohsen Pourmousa, Tomas Vaisar, Hyun D. Song, Richard W. Pastor, Alan T. Remaley, Ira J. Goldberg, Tina Costacou, W. Sean Davidson, Karin E. Bornfeldt, Laura Calabresi, Jere P. Segrest, Jay W. Heinecke
Journal: Circulation (2023)

BACKGROUND: Cholesterol efflux capacity (CEC) predicts cardiovascular disease independently of high-density lipoprotein (HDL) cholesterol levels. Isolated small HDL particles are potent promoters of macrophage CEC by the ABCA1 (ATP-binding cassette transporter A1) pathway, but the underlying mechanisms are unclear. METHODS: We used model system studies of reconstituted HDL and plasma from control and lecithin-cholesterol acyltransferase (LCAT)–deficient subjects to investigate the relationships among the sizes of HDL particles, the structure of APOA1 (apolipoprotein A1) in the different particles, and the CECs of plasma and isolated HDLs. RESULTS: We quantified macrophage and ABCA1 CEC of 4 distinct sizes of reconstituted HDL. CEC increased as particle size decreased. Tandem mass spectrometric analysis of chemically cross-linked peptides and molecular dynamics simulations of APOA1, the major protein of HDL, indicated that the mobility of C-terminus of that protein was markedly higher and flipped off the surface in the smallest particles. To explore the physiological relevance of the model system studies, we isolated HDL from LCAT-deficient subjects, whose small HDLs (like reconstituted HDLs) are discoidal and composed of APOA1, cholesterol, and phospholipid. Despite their very low plasma levels of HDL particles, these subjects had normal CEC. In both the LCAT-deficient subjects and control subjects, the CEC of isolated extra-small HDL (a mixture of extra-small and small HDL by calibrated ion mobility analysis) was 3- to 5-fold greater than that of the larger sizes of isolated HDL. Incubating LCAT-deficient plasma and control plasma with human LCAT converted extra-small and small HDL particles into larger particles, and it markedly inhibited CEC. CONCLUSIONS: We present a mechanism for the enhanced CEC of small HDLs. In smaller particles, the C-termini of the 2 antiparallel molecules of APOA1 are “flipped” off the lipid surface of HDL. This extended conformation allows them to engage with ABCA1. In contrast, the C-termini of larger HDLs are unable to interact productively with ABCA1 because they form a helical bundle that strongly adheres to the lipid on the particle. Enhanced CEC, as seen with the smaller particles, predicts decreased cardiovascular disease risk. Thus, extra-small and small HDLs may be key mediators and indicators of the cardioprotective effects of HDL.
Origami‐Inspired Bionic Soft Robot Stomach with Self‐Powered Sensing
Authors: Jinsui Xu, Boyi Xu, Honghao Yue, Zhijie Xie, Ye Tian, Fei Yang
Journal: Advanced Healthcare Materials (2023)

The stomach is a vital organ in the human digestive system, and its digestive condition is critical to human health. The physical movement of the stomach during digestion is controlled by the circular and oblique muscles. Existing stomach simulators are unable to realistically reproduce the physical movement of the stomach. Due to the complexity of gastric motility, it is challenging to simulate and sense gastric motility. This study proposes for the first time a bionic soft robotic stomach (BSRS) with an integrated drive and sensing structure inspired by origami and self-powered sensing technology. This soft stomach (SS) can realistically simulate and sense the movements of various parts of the human stomach in real-time. The contraction force and contraction rate of the BSRS are investigated with different viscosity contents, and the experimental values are similar to the physiological range (maximum contraction force is 3.2 N, and maximum contraction rate is 0.8). This paper provides an experimental basis for the study of gastric digestive medicine and food science by simulating the peristaltic motion of the BSRS according to the human stomach and by combining the triboelectric nanogenerator (TENG) sensing technology to monitor the motion of the BSRS in real-time.
Extracellular Matrix Disorganization Caused by ADAMTS16 Deficiency Leads to Bicuspid Aortic Valve With Raphe Formation
Authors: Ying Lin, Qifan Yang, Xiaoping Lin, Xianbao Liu, Yi Qian, Dilin Xu, Naifang Cao, Ximeng Han, Yanqing Zhu, Wangxing Hu, Xiaopeng He, Zhengyang Yu, Xiangmin Kong, Lianlian Zhu, Zhiwei Zhong, Kai Liu, Bin Zhou, Yidong Wang, Jinrong Peng, Wei Zhu, Jian’an Wang
Journal: Circulation (2023)

A better understanding of the molecular mechanism of aortic valve development and bicuspid aortic valve (BAV) formation would significantly improve and optimize the therapeutic strategy for BAV treatment. Over the past decade, the genes involved in aortic valve development and BAV formation have been increasingly recognized. On the other hand,
Decellularized extracellular matrix materials for treatment of ischemic cardiomyopathy
Authors: Wei Liu, Xiangmei Zhang, Xiaokai Jiang, Binyao Dai, Liwen Zhang, Yang Zhu
Journal: Bioactive Materials (2023)

Ischemic cardiomyopathy (ICM) affect millions of patients globally. Decellularized extracellular matrix materials (dECM) have components, microstructure and mechanical properties similar to healthy cardiac tissues, and can be manufactured into various forms of implantable biomaterials including injectable hydrogels or epicardial patches, which have been extensively reported to attenuate pathological left ventricular remodeling and maintain heart function. Recently, dECM medical devices for ICM treatment have been approved for clinical use or studied in clinical trials, exhibiting considerable translation potential. Cells, growth factors and other bioactive agents have been incorporated with different dECM materials to improve the therapeutic outcomes. In addition, more detailed aspects of the biological effects and mechanisms of dECM treatment are being revealed. This review summarized recent advances in dECM materials from variable sources for cardiac repair, including extraction of extracellular matrix, cell integration, smart manufacturing of injectable hydrogels and cardiac patch materials, and their therapeutic applications. Besides, this review provides an outlook on the cutting-edge development directions in the field.
Polyelectrolyte‐Cation Complexes Using PAsp‐Sr Complexes Induce Biomimetic Mineralization with Antibacterial Ability
Authors: Yuedan Xu, Dongni Shen, Zihuai Zhou, Yi Sun, Xinni Pan, Wei Liu, Chun Hung Chu, Ling Zhang, Matthias Hannig, Baiping Fu
Journal: Advanced Healthcare Materials (2023)

Abstract Remineralized dentin with an antibacterial ability is still a significant challenge in dentistry. Previously, a polyelectrolyte‐calcium complexes pre‐precursor (PCCP) process is proposed for rapid collagen mineralization. In the present study, the expansion concept of the PCCP process is explored by replacing the calcium with other cations, such as strontium. The results of transmission electron microscopy (TEM), 3D stochastic optical reconstruction microscopy, energy‐dispersive X‐ray analysis, Fourier transform infrared spectroscopy, and high‐resolution TEM with selected area electron diffraction demonstrate that biomimetic mineralization of collagen fibrils and demineralized dentin could be fulfilled with Sr&amp;F‐codoped hydroxyapatite (HAp) after they are treated with poly‐aspartic acid‐strontium (PAsp‐Sr) suspension followed by a phosphate&amp;fluoride solution. Moreover, dentin remineralized with Sr&amp;F‐codoped HAp exhibits in vitro and in vivo antibacterial ability against Streptococcus mutans . The cytotoxicity and oral mucosa irritation tests reveal excellent biocompatibility of mineralization mediums (PAsp‐Sr suspension and phosphate&amp;fluoride solution). The demineralized dentin's mechanical properties (elastic modulus and microhardness) could be restored almost to that of the intact dentin. Hence, the expansion concept of the PCCP process that replaces calcium ions with some cationic ions along with fluorine opens up new horizons for generating antibacterial remineralized dentin containing ions‐doped HAp with excellent biocompatibility via biomimetic mineralization technology.
Potential therapies targeting nuclear metabolic regulation in cancer
Authors: Yanjie Chen, Jie Xu, Xiaoyi Liu, Linlin Guo, Ping Yi, Chunming Cheng
Journal: MedComm (2023)

The interplay between genetic alterations and metabolic dysregulation is increasingly recognized as a pivotal axis in cancer pathogenesis. Both elements are mutually reinforcing, thereby expediting the ontogeny and progression of malignant neoplasms. Intriguingly, recent findings have highlighted the translocation of metabolites and metabolic enzymes from the cytoplasm into the nuclear compartment, where they appear to be intimately associated with tumor cell proliferation. Despite these advancements, significant gaps persist in our understanding of their specific roles within the nuclear milieu, their modulatory effects on gene transcription and cellular proliferation, and the intricacies of their coordination with the genomic landscape. In this comprehensive review, we endeavor to elucidate the regulatory landscape of metabolic signaling within the nuclear domain, namely nuclear metabolic signaling involving metabolites and metabolic enzymes. We explore the roles and molecular mechanisms through which metabolic flux and enzymatic activity impact critical nuclear processes, including epigenetic modulation, DNA damage repair, and gene expression regulation. In conclusion, we underscore the paramount significance of nuclear metabolic signaling in cancer biology and enumerate potential therapeutic targets, associated pharmacological interventions, and implications for clinical applications. Importantly, these emergent findings not only augment our conceptual understanding of tumoral metabolism but also herald the potential for innovative therapeutic paradigms targeting the metabolism-genome transcriptional axis.
The Long-Term Relationship Between Cannabis and Heroin Use: An 18- to 20-year Follow-Up of the Australian Treatment Outcome Study (ATOS)
Authors: Jack Wilson, Katherine L. Mills, Matthew Sunderland, Tom P. Freeman, Maree Teesson, Paul S. Haber, Christina Marel
Journal: American Journal of Psychiatry (2023)

Objective: Cannabis use is common among individuals with opioid use disorder, but it remains unclear whether cannabis use is associated with an increase or a reduction in illicit opioid use. To overcome limitations identified in previous longitudinal studies with limited follow-ups, the authors examined a within-person reciprocal relationship between cannabis and heroin use at several follow-ups over 18 to 20 years. Methods: The Australian Treatment Outcome Study (ATOS) recruited 615 people with heroin dependence in 2001 and 2002 and reinterviewed them at 3, 12, 24, and 36 months as well as 11 and 18–20 years after baseline. Heroin and cannabis use were assessed at each time point using the Opiate Treatment Index. A random-intercept cross-lagged panel model analysis was conducted to identify within-person relationships between cannabis use and heroin use at subsequent follow-ups. Results: After accounting for a range of demographic variables, other substance use, and mental and physical health measures, an increase in cannabis use 24 months after baseline was significantly associated with an increase in heroin use at 36 months (estimate=0.21, SE=0.10). Additionally, an increase in heroin use at 3 months and 24 months was significantly associated with a decrease in cannabis use at 12 months (estimate=−0.27, SE=0.09) and 36 months (estimate=−0.22, SE=0.08). All other cross-lagged associations were not significant. Conclusions: Although there was some evidence of a significant relationship between cannabis and heroin use at earlier follow-ups, this was sparse and inconsistent across time points. Overall, there was insufficient evidence to suggest a unidirectional or bidirectional relationship between the use of these substances.
Converging Evidence for Frontopolar Cortex as a Target for Neuromodulation in Addiction Treatment
Authors: Ghazaleh Soleimani, Juho Joutsa, Khaled Moussawi, Shan H. Siddiqi, Rayus Kuplicki, Marom Bikson, Martin P. Paulus, Michael D. Fox, Colleen A. Hanlon, Hamed Ekhtiari
Journal: American Journal of Psychiatry (2023)

Noninvasive brain stimulation technologies such as transcranial electrical and magnetic stimulation (tES and TMS) are emerging neuromodulation therapies that are being used to target the neural substrates of substance use disorders. By the end of 2022, 205 trials of tES or TMS in the treatment of substance use disorders had been published, with heterogeneous results, and there is still no consensus on the optimal target brain region. Recent work may help clarify where and how to apply stimulation, owing to expanding databases of neuroimaging studies, new systematic reviews, and improved methods for causal brain mapping. Whereas most previous clinical trials targeted the dorsolateral prefrontal cortex, accumulating data highlight the frontopolar cortex as a promising therapeutic target for transcranial brain stimulation in substance use disorders. This approach is supported by converging multimodal evidence, including lesion-based maps, functional MRI-based maps, tES studies, TMS studies, and dose-response relationships. This review highlights the importance of targeting the frontopolar area and tailoring the treatment according to interindividual variations in brain state and trait and electric field distribution patterns. This converging evidence supports the potential for treatment optimization through context, target, dose, and timing dimensions to improve clinical outcomes of transcranial brain stimulation in people with substance use disorders in future clinical trials.
Trends in Prevalence of Cannabis Use Disorder Among U.S. Veterans With and Without Psychiatric Disorders Between 2005 and 2019
Authors: Ofir Livne, Carol A. Malte, Mark Olfson, Melanie M. Wall, Katherine M. Keyes, Charles Maynard, Jaimie L. Gradus, Andrew J. Saxon, Silvia S. Martins, Salomeh Keyhani, Yoanna McDowell, David S. Fink, Zachary L. Mannes, Sarah Gutkind, Deborah S. Hasin
Journal: American Journal of Psychiatry (2023)

Cannabis use disorder diagnoses are increasing among U.S. adults and are more prevalent among people with comorbid psychiatric disorders. Recent changes in cannabis laws, increasing cannabis availability, and higher-potency cannabis may have placed people with cannabis use and psychiatric disorders at disproportionately increasing risk for cannabis use disorder. The authors used Veterans Health Administration (VHA) data to examine whether trends in cannabis use disorder prevalence among VHA patients differ by whether they have psychiatric disorders.
New discoveries on how DICER efficiently processes pre‐miRNA
Authors: Qi Weng, Qi Wu, Quan Zheng
Journal: MedComm (2023)

The latest study identified the "GYM motif" on precursor microRNA (pre-miRNA) for the first time and highlighted its key role in DICER specifically recognizing and efficiently cleaving pre-miRNA to produce miRNA. In addition, the dicing state of DICER efficiently processing pre-miRNA was revealed, which was previously difficult to capture.
Unveiling <i>Candida albicans</i> intestinal carriage in healthy volunteers: the role of micro- and mycobiota, diet, host genetics and immune response
Authors: Margot Delavy, Natacha Sertour, Etienne Patin, Emmanuelle Le Chatelier, Nathaniel Cole, Florian Dubois, Zixuan Xie, Violaine Saint-André, Chaysavanh Manichanh, Alan W. Walker, Lluis Quintana-Murci, Darragh Duffy, Christophe d’Enfert, Marie-Elisabeth Bougnoux, Milieu Intérieur Consortium
Journal: Gut Microbes (2023)

Candida albicans is a commensal yeast present in the gut of most healthy individuals but with highly variable concentrations. However, little is known about the host factors that influence colonization densities. We investigated how microbiota, host lifestyle factors, and genetics could shape C. albicans intestinal carriage in 695 healthy individuals from the Milieu Intérieur cohort. C. albicans intestinal carriage was detected in 82.9% of the subjects using quantitative PCR. Using linear mixed models and multiway-ANOVA, we explored C. albicans intestinal levels with regard to gut microbiota composition and lifestyle factors including diet. By analyzing shotgun metagenomics data and C. albicans qPCR data, we showed that Intestinimonas butyriciproducens was the only gut microbiota species whose relative abundance was negatively correlated with C. albicans concentration. Diet is also linked to C. albicans growth, with eating between meals and a low-sodium diet being associated with higher C. albicans levels. Furthermore, by Genome-Wide Association Study, we identified 26 single nucleotide polymorphisms suggestively associated with C. albicans colonization. In addition, we found that the intestinal levels of C. albicans might influence the host immune response, specifically in response to fungal challenge. We analyzed the transcriptional levels of 546 immune genes and the concentration of 13 cytokines after whole blood stimulation with C. albicans cells and showed positive associations between the extent of C. albicans intestinal levels and NLRP3 expression, as well as secreted IL-2 and CXCL5 concentrations. Taken together, these findings open the way for potential new interventional strategies to curb C. albicans intestinal overgrowth.
The gut-joint axis mediates the TNF-induced RA process and PBMT therapeutic effects through the metabolites of gut microbiota
Authors: Qingtai Meng, Monan Lin, Wuqi Song, Jiahui Wu, Guoding Cao, Ping Huang, Zaiyu Su, Wei Gu, Xueqing Deng, Peng Xu, Yi Yang, Hui Li, Hailiang Liu, Fengmin Zhang
Journal: Gut Microbes (2023)

The gut-joint axis, one of the mechanisms that mediates the onset and progression of joint and related diseases through gut microbiota, and shows the potential as therapeutic target. A variety of drugs exert therapeutic effects on rheumatoid arthritis (RA) through the gut-joint axis. However, the anti-inflammatory and immunomodulatory effect of novel photobiomodulatory therapy (PBMT) on RA need further validation and the involvement of gut-joint axis in this process remains unknown. The present study demonstrated the beneficial effects of PBMT on RA, where we found the restoration of gut microbiota homeostasis, and the related key pathways and metabolites after PBMT. We also discovered that the therapeutic effects of PBMT on RA mainly through the gut-joint axis, in which the amino acid metabolites (Alanine and N-acetyl aspartate) play the key role and rely on the activity of metabolic enzymes in the target organs. Together, the results prove that the metabolites of amino acid from gut microbiota mediate the regulation effect on the gut-joint axis and the therapeutic effect on rheumatoid arthritis of PBMT.
Gut feelings: the relations between depression, anxiety, psychotropic drugs and the gut microbiome
Authors: S. Brushett, R. Gacesa, A. Vich Vila, M.F. Brandao Gois, S. Andreu-Sánchez, J.C. Swarte, M.A.Y. Klaassen, V. Collij, T. Sinha, L.A. Bolte, J. Wu, M. Swertz, M.L.A. de Kroon, S.A. Reijneveld, C. Wijmenga, R.K. Weersma, J. Fu, H.M. van Loo, A. Kurilshikov, A. Zhernakova
Journal: Gut Microbes (2023)

The gut microbiome is involved in the bi-directional relationship of the gut – brain axis. As most studies of this relationship are small and do not account for use of psychotropic drugs (PTDs), we explored the relations of the gut microbiome with several internalizing disorders, while adjusting for PTDs and other relevant medications, in 7,656 Lifelines participants from the Northern Netherlands (5,522 controls and 491 participants with at least one internalizing disorder). Disorders included dysthymia, major depressive disorder (MDD), any depressive disorder (AnyDep: dysthymia or MDD), generalized anxiety disorder (GAD) and any anxiety disorder (AnyAnx: GAD, social phobia and panic disorder). Compared to controls, 17 species were associated with depressive disorders and 3 were associated with anxiety disorders. Around 90% of these associations remained significant (FDR <0.05) after adjustment for PTD use, suggesting that the disorders, not PTD use, drove these associations. Negative associations were observed for the butyrate-producing bacteria Ruminococcus bromii in participants with AnyDep and for Bifidobacterium bifidum in AnyAnx participants, along with many others. Tryptophan and glutamate synthesis modules and the 3,4-Dihydroxyphenylacetic acid synthesis module (related to dopamine metabolism) were negatively associated with MDD and/or dysthymia. After additional adjustment for functional gastrointestinal disorders and irritable bowel syndrome, these relations remained either statistically (FDR <0.05) or nominally (P < 0.05) significant. Overall, multiple bacterial species and functional modules were associated with internalizing disorders, including gut – brain relevant components, while associations to PTD use were moderate. These findings suggest that internalizing disorders rather than PTDs are associated with gut microbiome differences relative to controls.
Overexpression of ABCC1 and ABCG2 confers resistance to talazoparib, a poly (ADP-Ribose) polymerase inhibitor
Authors: Qiu-Xu Teng, Zi-Ning Lei, Jing-Quan Wang, Yuqi Yang, Zhuo-Xun Wu, Nikita Dilip Acharekar, Wei Zhang, Sabesan Yoganathan, Yihang Pan, John Wurpel, Zhe-Sheng Chen, Shuo Fang
Journal: Drug Resistance Updates (2023)